Background Synapses and spines are central in major depressive disorder (MDD) pathophysiology, recently highlighted by ketamine’s and psilocybin’s rapid antidepressant effects. The Bayesian brain and interoception perspectives formalize MDD as being “stuck” in affective states constantly predicting negative energy balance. We examined how synaptic atrophy re...
Clinical studies provide evidence that ketamine and psilocybin could be used as fast-acting antidepressants, though their mechanisms and toxicity are still not fully understood. To address this issue, we have examined the effect of a single administration of ketamine and psilocybin on the extracellular levels of neurotransmitters in the rat frontal cortex an...
Psilocybin has been shown to be a powerful, long-lasting antidepressant in human clinical trials and in rodent models. Although rodents have commonly been used to model psychiatric disorders, Drosophila have neurotransmitter systems similar to mammals and many comparable brain structures involved in similar behaviors. The forced swim test (FST), which has be...
Abstract Psychedelic substances such as psilocybin and ketamine may represent the future of antidepressant treatment, due to their rapid and prolonged effects on mood and cognition. The current body of psychedelic research has focused on administration and treatment within a psychiatric context. Here, instead, we put to the test the contention that it is nec...
Recent trials with psychedelics in major depressive disorder and treatment-resistant depression showed remarkable improvements in depressive symptoms that can last for up to several months after even a single administration. The lack of an appropriate placebo control group-as patients are often able to discriminate the subjective effects of the drug-and an i...
Back to table of contents Previous article Next article Clinical & ResearchFull AccessPsilocybin-Assisted Therapy Found to Improve Depression, Offer Other BenefitsRichard KarelRichard KarelSearch for more papers by this authorPublished Online:23 May 2022https://doi.org/10.1176/appi.pn.2022.06.6.30AbstractA small study involving 24 participants found that psi...
The main goal is to compare the antidepressant effects of psilocybin and ketamine in patients with TRD versus the antidepressant inactive substance midazolam. The primary endpoint will be the antidepressant effect on the Montgomery- Asberg Depression Rating Scale (MADRS) 24 hours after treatment, the key secondary endpoints being the duration of antidepressa...
Effects of serotonin 2A/1A receptor stimulation by psilocybin on mood and emotion processing in major depressive disorder: a randomized double-blind placebo-controlled study Major depressive disorder (MDD) is one of the world's greatest contributor to the global burden of disease and MDD affects around 17% of the Swiss population (Tomonaga et al. 2013). It i...
IntroductionA limited number of preliminary open-label (n = 3) and placebo-controlled clinical trials (n = 5) have suggested psilocybin and LSD as potential rapid antidepressants. In this context, there is a growing need to verify and document their safety and tolerability as therapeutic agents, discuss the challenges associated with their administration, an...
Psilocybin therapy shows antidepressant potential, but its therapeutic actions are not well understood. We assessed the subacute impact of psilocybin on brain function in two clinical trials of depression. The first was an open-label trial of orally administered psilocybin (10 mg and 25 mg, 7 d apart) in patients with treatment-resistant depression. Function...
Back to table of contents Previous article Next article Annual MeetingFull AccessDemystifying Psychedelic Treatments in Psychiatry: Is Ego Dissolution the Solution?Michael Avissar, M.D., Ph.D., Adrian Jacques Ambrose, M.D., M.P.H.Michael AvissarSearch for more papers by this author, M.D., Ph.D., Adrian Jacques AmbroseSearch for more papers by this author, M....
Promising outcomes of Psilocybin-Assisted Therapy (PAT) for depression have generated concerted efforts to replicate, extend, and refine protocols to maximize efficacy. Psychotherapy research reveals that clients benefit most when important components of treatment align with their personal preferences. One open question related to PAT concerns the importance...
Mushrooms have been used as traditional medicine for millennia, fungi are the main natural source of psychedelic compounds. There is now increasing interest in using fungal active compounds such as psychedelics for alleviating symptoms of mental health disorders including major depressive disorder, anxiety, and addiction. The anxiolytic, antidepressant and a...
RationaleKetamine and psilocybin belong to the rapid-acting antidepressants but they also produce psychotomimetic effects including timing distortion. It is currently debatable whether these are essential for their therapeutic actions. As depressed patients report that the "time is dragging," we hypothesized that ketamine and psilocybin-like compounds may pr...
Serotonergic psychedelic drugs, such as psilocin (4-hydroxy-N,N-dimethyltryptamine), profoundly alter the quality of consciousness through mechanisms which are incompletely understood. Growing evidence suggests that a single psychedelic experience can positively impact long-term psychological well-being, with relevance for the treatment of psychiatric disord...
We examined the cardiovascular safety, acceptability, and trajectory of the antidepressant effects of psilocybin after single- or two-dose administration. Four major electronic databases were systematically searched. Data were pooled using a multivariate random-effects meta-analysis. Primary outcomes were changes in depressive symptoms. Secondary outcomes we...
Scientists have long sought the secrets of the 5-HT2A serotonin receptor-a central nervous system receptor that binds hallucinogenic compounds, including LSD and psilocybin. Many hope to discover why these molecules cause hallucinations when they bind to 5-HT2A while other compounds that bind to the receptor, including serotonin, do not. LSD and psilocybin h...
BackgroundPreliminary data suggest that psilocybin-assisted treatment produces substantial and rapid antidepressant effects in patients with major depressive disorder (MDD), but little is known about long-term outcomes.AimsThis study sought to examine the efficacy and safety of psilocybin through 12 months in participants with moderate to severe MDD who rece...
BackgroundPsychedelics, such as psilocybin represent one of the most promising current therapeutic approaches in psychiatry.ObjectivePsychedelics seem to have not only potent antidepressant effects. Do they also work particularly quickly, i.e. within one day?Material and methodsThe available literature on clinical studies of psychedelics in depressive syndro...
Drugs that target the human serotonin 2A receptor (5-HT2AR) are used to treat neuropsychiatric diseases; however, many have hallucinogenic effects, hampering their use. Here, we present structures of 5-HT2AR complexed with the psychedelic drugs psilocin (the active metabolite of psilocybin) and d-lysergic acid diethylamide (LSD), as well as the endogenous ne...
